DESCRIPTION: (Applicant's Abstract) Since the inception of the Human Genome Program in 1990, it has become increasingly apparent that a broad range of advances in biomedical research can be dramatically accelerated by the provision of genomic sequence information from model organisms. To date, the genomes of several model organisms (baker's yeast, the roundworm and the fruit fly) have been completely sequenced and have provided many insights into the ways in which various cellular processes take place. The rat is a model organism used widely in studies of common diseases such as high blood pressure, drug and alcohol addiction and cancer. A complete rat genome will be immensely valuable in helping to understand the genetic basis of such important diseases in humans. Using a combination of a new generation of automated DNA sequencing machines, an industrial approach to high-throughput DNA sequencing and advanced computational techniques, Celera Genomics has developed the world's most productive genome sequencing facility. With a sequencing strategy that is known as whole genome shotgun sequencing, an efficient means of determining large amounts of DNA sequence while providing comprehensive coverage of the genome, Celera has determined the sequence of the Drosophila and human genomes and has a mouse genome program well underway. With its experience in efficient and cost-effective high-throughput DNA sequencing, Celera here proposes to perform whole genome shotgun sequencing of the rat genome, providing an average three-fold coverage. Sequencing would be performed with an equal mix of 2 kb and 10 kb clones from random whole genome libraries. In addition to its unmatched sequencing capacity, Celera has developed the most advanced computational algorithms and infrastructure for genome assembly, the process needed to put together the individual sequence fragments produced by the shotgun sequencing process into continuous stretches of genomic DNA sequence, and will undertake the assembly of the sequence that it produces together with any sequence produced by other members of a rat genome sequencing initiative. As a key member of the rat genome sequencing initiative, Celera intends to create a public whole genome assembly for the rat by integrating whole-genome shotgun data produced at Celera with BAC-end sequence data and light shotgun data from mapped BACs produced at other participating centers.